Academic lectures for students GENERAL of medical schools – 3rd Year PATHOPHYSIOLOGY updated 2004 - 201 5 NEOPLASMS 1 CLINICAL PATHOLOGY R. A. Benacka, MD, PhD Department of Pathophysiology Faculty of Medicine, UPJS, Slovakia Templates, figures and tables herein might be adapted from various printed or electornic resources and serve strictly for educational purposes and pro bono of mankind Epidemiology Incidency of neoplasms Mortality of neoplasms Age related types of tumours Neoplasms - history Evidences of bone tumors were found in prehistoric remains of homo sapiens and predestors. Description of disease found in early writings from India, Egypt, Babylonia, and Greece . Hippocrates distinguished benign from malignant growths; introduced the term karkinos (in Latin cancer ) presumably because a cancer adheres to any part that it seizes upon in an obstinate manner like the crab. Hippocrates described in detail cancer of the breast , and in the 2nd century AD, Paul of Aegina commented on its frequency. Over the decades paleoarchaeologists have made about 200 possible cancer sightings dating to prehistoric times. The Karkinos was giant crab which oldest known case of metastasizing prostate cancer was found came to the aid of the hydra in in Scythian burial mound in the Russian region of Tuva. battle against Hérakles Terminology comes form greek and latin words: Neoplasia - the process of "new growth," and a new growth is called a neoplasm. Tumor - originally applied to the swelling caused by inflammation. Neoplasms also may induce swellings. Non- neoplastic usage of tumor has passed; the term is now equated with neoplasm. Oncology (Greek oncos = tumor) - the study of tumors. Cancer is the common term for all malignant tumors. 14.1 million new cancer cases, 8.2 million cancer deaths and 32.6 million people living with cancer (within 5 years of diagnosis) in 2012 worldwide. Incidence in underdeveloped regions not too higher: 57% of new cancer cases, 65% of the cancer deaths The overall age standardized cancer incidence rate is 25% higher in men than in women, with rates of 205 and 165 per 100,000, respectively . Male incidence rates vary 5x : 79/100,000 in Western Africa to 365/100,000 in Australia . F emale incidence varie 3x : 103 / 100,000 in South-Central Asia to 295/ 100,000 in Northern America. In men, the rates is highest in Central and Eastern Europe (173 per 100,000) and lowest in Western Africa (69). In contrast, the highest rates in women are in Melanesia (119) and Eastern Africa (111), and the lowest in Central America (72) and South-Central (65) Asia. Incidency of neoplasms in US Conclusions • Incidence of neoplastic disease increases with age. But there are age-related specific tumors Overall incidence of cancer increased because of greater longevity in modern times In past humans died mostly from infectious diseases, did not live long enough to develop cancers of middle and old age Spectrum of cancers remains likely the same over the time Occurrence of particular forms of cancer change with age Tumors of uterus, stomach, liver decresed over half-century other other like ovary, prostate breast, pancreas remain little changed, tumour of liver and leukemia returned. Lung cancer is clearly on the sustained rise mainly in women . Estimated Cancer Incidence Worldwide : Men Resource : http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx Estimated age-standardised rates (World) per 100,000 Estimated Cancer Incidence Worldwide : Women Resource : http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx Estimated age-standardised rates (World) per 100,000 Cancer incidency and death rate by site and sex No increase in age-adjusted cancer death rate in men in the past 50y. Continually decreasing rate in women. Death rate of lung cancer in humans (women and men in average) is ~ 2x higher than any other cancer The incidence of breast cancer is ~ 2x higher than any other cancer in women; incidence of prostate cancer is ~ 2x higher than any other cancer in men. Occurence of tumors before 20th year of life Up to 40% of tumors in childhood are haematological – leukemias and lymphomas; cca 30 % are tumors of CNS (brain and spinal cord; 6-7% from that is neuroblastoma, kidney tumors 5-6%, tumors of bones 5%, tunmors from muscles (rhamdomyosarcoma) 4%, retinoblastoma 3%. Cancer of testes and ovaries represent 13 % in postpubertal age, melanomas and skin carcinoma up to 20%, around 30% are hematological and 19% brain tumors. Specific tumors mportality Lung cancer most common – and deadliest – cancer in the world, with an estimated 1.8 million new cases and 1.59 million deaths in 2012; going up for women and down for men smoking rates is highest in Central and Eastern Europe (53.5 new cases per 100,000 people in 2012), and lowest in West Africa (1.7 new cases per 100,000) Cervical cancer - women Fourth-most common cancer in women, with an estimated 528,000 new cases and 266,000 deaths in 2012; women in the developing world show 10x higher death rate ; Finland - introduced the best cervical-cancer screening program in the world; human papillomavirus, or HPV vacination Liver cancer Second-most common cause of cancer death around the world ; associated with hepatitis B, alcohol Asia - Mongolia, Laos, Vietnam, Cambodia, Thailand and China top 10 countries for liver-cancer deaths, Mongolia - highest cancer mortality rate of any country (161 deaths per 100,000 people) Hepatitis B vaccination program after birth in China; Canada logged 3.6 new cases of liver cancer and 3.3 deaths per 100,000 people in 2012. Breast cancer - women The most common cancer in women (1.7 million new cases in 2012 and 522,000 deaths); 1,8 million new cases in 2015 and 423,000 deaths = decrease 5 % over 10 years Increased 20 % since 2008: perfect diagnostics in Europe (90 new cases per 100,000 women); no screening in East Africa (30 per 100,000 women) weak screening in Asia (42 per 100,000 women) ; The highest proportion in Western Europe – Belgium, Denmark and France; highest mortality rates in Fiji, Bahamas and Nigeria Prostatic cancer - men The most frequently diagnosed cancer among men ~ 88.9 new cases for 100,000 men; 3rd in mortality: ~ 9.4 per 100,000 North America and ~ 8,3 per 100,000 in Europe Prostate-specific antigen (PSA) blood test has made early detection and treatment Aggressive testing campaigns have raised concerns that prostate cancer is being overly diagnosed Prostate cancer is deadlier in Caribbean men (29 per 100,000 men) and sub-Saharan Africa (24 per 100,000 men) Characteristics of the tumor cells Benign tumors Malignant tumors General considerations Tumors are genetic, mostly non-hereditary disorders , which develop due to specific mutations in the specific genes of the somatic cells (less commonly in germ cells). These specific genes those regulating cell growth ( cell cycle movement in response to mitogenic signals, DNA repair and apoptosis) Tumorigenic mutations must render them the capacity to grow and multiply in excess of other cell, and to do that autonomously , irrespective of body needs. Not every mutation in above genes is tumorigenic (neoplastic ); actually, most of them are out of effect or, on contrary, they induce degradation, or atrophy Neoplasms are derived from cells that normally maintain a proliferative capacity ( i.e. mature neurons and cardiac myocytes do not give rise to tumors). In general, neoplasms are irreversible. Tumors do not develop overnight ; it is mutlistep long-term progress . Unfortunately, we are not aware of that, only in time when tumor is manifested clinically, i.e. when tumor contains ~ 10 9 cells. Tumorigenesis may be common.. Many tumors are eradicated by immunological surveilance A tumor may express varying degrees of differentiation , from relatively mature structures that mimic normal tissues to a collection of cells so primitive that the cell of origin cannot be identified. The stimulus (exact reason) responsible for the uncontrolled proliferation may not be identifiable; in fact, it is not known for most human neoplasms. All tumors are typical by overgrowth`forming local mass, and either non invasive growth respecting the borders and surroudung structure or invasive growth – outgrowing of finger like processes in star like appearance Comparison of benign and malignant tumors Benign and malignant tumours BENIGN TUMORS MALIGNANT TUMORS Benign tumors are histologically similar to their Malignant neoplasms range from well differentiated tissues of origin, their growth is slow types into undifferentiated ones , well-differentiated The gross structure of a benign tumor may depart cancer evolves from maturation or specialization of from the normal and/or papillary or polypoid dedifferentiated cells as they proliferate configurations (papillomas of the bladder and skin undifferentiated malignant tumor (anaplastic) derives and adenomatous polyps of the colon). from proliferation without complete maturation of the Benign tumor are inable to invade into adjacent transformed cells. tissue and inable to metastasize. Malignant tumor s are ab le to invade into adjacent tissue Benign tumors are circumscribed by a connective and able to metastasize tissue capsule , many benign neoplasms are not Many cancers arise from stem cells that are present in all encapsulated (papillomas and polyps, hepatic specialized tissues and do not represent "reverse adenomas, many endocrine adenomas, and differentiation" of mature normal cells hemangiomas. Changes in cell phenotype towards a cancer Prosoplasia